The application of microorganisms for in situ delivery of therapeutics was first demonstrated by (Steidler et al. 2000) with lactic acid bacteria. The cheese bacterium Lactococcus lactis was engineered to secrete murine interleukin-10 (mIL10). Oral administration of the recombinant lactic acid bacterium significantly reduced intestinal inflammation in two mouse models of disease. The authors demonstrated mIL-10 was detected in the colon of IL10−/− mice and that the therapeutic effect was obtained following de novo synthesis of IL-10 by L. lactis during gastrointestinal (GI) transit. Since then, the L. lactis workhorse has been exploited to deliver a variety of recombinant proteins (Bahey-El-Din et al. 2010, Robert et al., 2014) and DNA (Guimarães et al. 2009, Chatel et al. 2008, de Azevedo et al., 2012), and has paved the way to harness other microbes as delivery vehicles. In particular, engineering food-grade microorganisms that can survive passage through the gastrointestinal tract, and naturally encode health-promoting properties, collectively provides a promising platform to deliver biologics of interest.
There are at least two challenges, however, to using microorganisms as biologic delivery vehicles. A first challenge is obtaining specificity in the delivery of biologics at therapeutic amounts, either with respect to particular sites in the body or within particular timeframes after administration. A second challenge is biologically containing the microorganisms. Biologic delivery vehicles that address these challenges are needed.